Adult survivors of childhood cancer at increased risk for late pulmonary complications

Survivors of childhood cancer face pulmonary complications long after initial diagnosis, resulting in limited daily activity and poorer quality of life, according to a report from the Childhood Cancer Survivor Study.

Despite improved survival rates, late mortality among childhood cancer survivors from pulmonary events — including lung fibrosis, chronic cough and exercise-induced dyspnea — continues to increase up to 25 years after diagnosis among those treated with chemotherapy, radiation or both.

“An understanding of the specific long-term risks to pulmonary health for survivors of childhood cancer will help to refine guidelines for appropriate screening and surveillance, promote health counseling, and, we hope, contribute to the design and testing of targeted interventions to decrease pulmonary morbidity and mortality for future cancer survivors,” Andrew C. Dietz, MD, MSCR, attending physician in the department of hematology, oncology, and blood and marrow transplantation at Center for Childhood Cancer and Blood Diseases of Children’s Hospital Los Angeles, and colleagues wrote.

The researchers used data from the Childhood Cancer Survivor Study to evaluate the incidence of pulmonary outcomes — including asthma, chronic cough, emphysema, lung fibrosis, oxygen need and recurrent pneumonia — and the incidence of death due to pulmonary causes among 14,316 survivors compared with 4,027 of their sibling controls.

The median age of survivors was 7 years (range, 0-21) at diagnosis and 32 years (range, 6-59) at evaluation. Median time form diagnosis was 25 years (range, 5-39).

By the age of 45 years, cumulative incidence of any pulmonary condition was 29.6% (95% CI, 29.1-30) in cancer survivors and 26.5% (95% CI, 24.9-28) of sibling controls.

Although fewer survivors reported ever smoking (23.6% vs. 36.4%; P < .001), they appeared more likely than controls to develop new onset chronic cough (rate ratio [RR] = 1.6; 95% CI, 1.4-1.9), need oxygen (RR = 1.8; 95% CI, 1.5-2.2), have lung fibrosis (RR = 3.5; 95% CI, 2.3-5.4) and have recurrent pneumonia (RR = 2; 95% CI, 1.4-3).

Pulmonary conditions also lead to greater limitations in daily activity among survivors compared with controls with the same pulmonary conditions. For instance, the likelihood for limited daily activity was greater among survivors with chronic cough (survivors, OR = 2.7; 95% CI, 2.4-3.1; controls, OR = 2; 95% CI, 1.5-2.6), oxygen need (survivors, OR = 3; 95% CI, 2.7-3.4; controls, OR = 2.3; 95% CI, 1.6-3.1) and recurrent pneumonia (survivors, OR = 3.2; 95% CI, 2.6-4; controls, OR = 1.8; 95% CI, 1-3.4).

“While often asymptomatic, damage to the lungs may limit activities of daily living with potential impact on the overall quality of life,” Dietz said in press release issued by the Children’s Hospital Los Angeles.

Death due to pulmonary cause occurred in 138 survivors. Researchers noted pulmonary cause–related deaths increased with longer time since diagnosis, exceeding 0.5% by 35 years after diagnosis.

Death due to pulmonary cause was associated with exposure to platinum-based agents (RR = 6.9; 95% CI, 1.8-27.3) and higher lung radiation dose, ranging from 10 Gy to less than 15 Gy (RR = 6.9; 95% CI, 1.8-27.3) to 25 Gy or more (RR = 15.7; 95% CI, 3.7-65.5).

The researchers acknowledged the study may have been limited by self-reported outcomes and overlap among outcomes.

Dietz and colleagues recommended that future prospective studies follow self-reported pulmonary events, measure changes in lung function and examine potential biomarkers to assist in earlier detection of pulmonary outcomes.

“This study adds to our understanding of specific, long-term risks to pulmonary health for survivors of childhood cancer, and will help refine guidelines for appropriate screening, health surveillance and counseling,” Daniel A. Mulrooney, MD, MS, assistant member of faculty in the oncology department at St. Jude Children’s Research Hospital, said in the press release. – by Kristie L. Kahl

Disclosure: The researchers report no relevant financial disclosures.